Sleep, Shift work and the COVID-19 vaccine immune Response Efficacy

COVID-19 pandemic is a global crisis, with devastating health, social and
economic impacts. To overcome this pandemic, there is a pressing need for safe
and effective vaccination programs. Growing evidence suggest that adequate
sleep can enhance the immune responsiveness to vaccination. Studies have shown
that sleep deprivation on several consecutive nights prior to and immediately
after Influenza and Hepatitis A/B vaccinations were associated with decreased
antibody formations.
In this innovative study we will investigate whether lack of sleep plays an
important role in the immune response to the COVID-19 vaccination.
Particularly, we focus on shift workers in the health care field, a vulnerable
population facing chronic sleep deprivation and circadian misalignment. We
hypothesize that the presence of recent night shifts and diminished sleep will
alter the immune response to vaccination in shift workers compared to day
workers.

Primary objective
The key objective is to examine the anti-body immune response to SARS-CoV-2
vaccination in shift workers, compared to dayworkers,

Secondary objectives:
• To tinvestigate whether sleep duration, independent of circadian
misalignment, is associated with the anti-body response after COVID-19
vaccination in dayworkers.
• To investigate the use of gut microbiome composition as a predictive
biomarker for vaccination efficacy.
• To determine the relation between sleep and long term anti-SARS-CoV-2 immune
responses over time in shift workers and dayworkers.
• To evaluate anti-SARS-CoV-2 specific T-cell responses in shift workers and
dayworkers.
• To assess adverse reactions after SARS-CoV-2 vaccination.

In this observational study blood will be drawn at 6 time points, i.e. baseline
(just before 1st vaccination), *10 days after the 1st vaccination, at the day
of 2nd vaccination, 28 days, 6 months and 12 months after 2nd vaccination.
These timepoints are used in all current Dutch COVID-19 vaccination trials to
make comparisons easier. Actigraphy and daily sleep e-diaries are administered
for 7 days around each vaccination to assess sleep. Short questionnaires will
be used to monitor sleep over time and to monitor for adverse reactions after
each vaccination. Last, fecal samples will be collected at baseline and*10 days
after 1st vaccination.

All participants will be vaccinated as part of the national vaccination
program, to which our observational study will be connected. Participants will
be asked to draw blood 6 times, collect 2 fecal samples, and wear an Actiwatch
and complete e-diaries for 7 days around the vaccination timepoints. These
activities are low risk and with minimal burden. Understanding the relation
between sleep, circadian misalignment and anti-body responses to the Covid-19
vaccine will be of outmost importance for global health.